-Introduction. Fruits are under growing scrutiny regarding their environmental impacts. However, fruit cropping systems have seldom been studied using life cycle assessment (LCA). As part of the Agribalyse project, the cropping systems for apple and peach in France, clementine in Morocco, and mango in Brazil were evaluated with a cradle-to-farm-gate LCA in order to include the manufacturing, transportation and utilization of all inputs used on the farm. Materials and methods. Representative systems for each fruit were designed, relying mostly on expert knowledge for apple, peach and clementine, and on a detailed survey of eight commercial orchards for mango from the Rio San Francisco Valley in Brazil. Potential environmental impacts were calculated using the ReCiPe Midpoint (H) method. Results and discussion. For most impact categories, apple showed the least impacts, followed by mango, peach and clementine. For marine eutrophication, mango and small citrus had the least impact, followed by apple and peach far above. For ecotoxicity, mango had the least impact followed by apple, peach and clementine far above. For each fruit cropping system, margins of improvement were identified and associated with agronomic recommendations. Generally speaking, the key aspects driving the eco-efficiency of fruit cropping systems at the farm gate were the yield, the fertilizer rates, the use of toxic substances for pest management, the water requirement associated with its local availability and the energy source for irrigation. The ecotoxicity results revealed were uncertain due to the difficulty of determining representative crop protection practices for perennial crops. Conclusion. The Agribalyse program represented an important step forward for the environmental assessment of fruits. Complementary research is needed to design better crop protection practices, field emissions and water-use impacts.Résumé -Impacts environnementaux des fruits importés ou cultivés localement pour le marché français : ACV du berceau à la porte de la ferme. Introduction. L'attention portée aux impacts environnementaux associés à la production fruitière est grandissante. Pourtant, les systèmes de culture fruitiers ont rarement été étudiés par l'analyse du cycle de vie (ACV). Dans le cadre du projet Agribalyse , les systèmes de production de pommes et de pêches en France, de clémentines au Maroc et de mangues au Brésil ont été évalués avec l'ACV du berceau à la porte de la ferme, afin de prendre en compte la fabrication, l'acheminement et l'utilisation de tous les intrants utilisés sur l'exploitation agricole. Matériel et méthodes. Un système représentatif pour chaque fruit a été conçu en se basant principalement sur les connaissances d'experts en pomme, pêche et clémentine et sur une enquête détaillée de huit vergers commerciaux de mangue dans la vallée du Rio San Francisco au Brésil. Les impacts environnementaux potentiels ont été calculés en utilisant la méthode ReCiPe (H) Midpoint. Résultats et discussion. Pour la plupart des catégories...
Background CRS (Cytokine Release Syndrome) is considered as a recurrent side effect of CAR (Chimeric Antigen Receptor) T cell therapy. An experimental animal model for better investigating different aspects of CRS is still in demand. Besides CAR T cells`astonishing achievements, numerous efforts are determined on manufacturing hindrance, notably shortening production procedures. Here, we introduce a novel CRS mouse model employing the NSG-SGM3 strain to address adverse effects of FT-CAR T cells (Fast-Track CAR T). Methods CD19-specific FT-CAR T cells were produced from 48 hours activated human PBMC plus 24h incubation with lentiviral vectors (LV). Cytotoxic activity of FT-CAR T cells was determined against Nalm-6 cells +/-same donor-derived monocyte supplementation allowed in vitro CRS assessment. Next, to launch a CRS mouse model, FT-CAR T cells were administered into NSG-SGM3 mice engrafted with Nalm-6 cells. Mice received 1x10 7 FT-CAR or activated T cells intravenously. Health condition assessment and body index calculation were regularly monitored using weight, and body temperature measurements. Human cytokines in plasma were determined by the LEGENDplex kit.Results Flow cytometric analysis revealed that the majority of FT-CAR T cells were positive for the VSV-glycoprotein. Upon reactivation and further cultivation, 65% of all T cells converted into CAR-positive T cells by day 6. The FT-CAR T cells indicated significant cytotoxic activity against tumor cells compared to T cell control, without any contraction in presence of monocytes. The co-culture supernatant displayed significantly elevated amounts of pro-inflammatory cytokines, including IL-6, INF-g, TNF-a, and IL-10. Next, we appointed the NSG-SGM3 mice to refine FT-CAR T cell competence in CRS induction. While all control mice were in good condition, detrimental side effects came up rapidly within 24h for all FT-CAR T-treated mice. Tremendous temperature change over 2°C and more than 10% weight loss led to termination of this group. Highly elevated cytokine levels were observed, notably enhanced for IFN-g, TNF-a, IL-2, IL-10 (all P<0.0001), and IL-6 (P<0.0121). Conclusions Our study introduces an appropriate CRS mouse model to substantiate the acute side effects of FT-CAR T cells.The key feature of this model is innate myeloid cells releasing cytokines upon interaction with CAR T cells. Our results suggest that FT-CAR T cells carry residual LV components and can induce at least as severe CRS as conventional CAR T cells.
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